Pierre Blanchard, Anne W.M. Lee, Alexandra Carmel, Ng Wai Tong, Jun Ma, Anthony T.C. Chan, Ruey Long Hong, Ming-Yuan Chen, Lei Chen, Wen-Fei Li, Pei-Yu Huang, Dora L.W. Kwong, Sharon S.X. Poh, Roger Ngan, Hai-Qiang Mai, Camille Ollivier, George Fountzilas, Li Zhang, Jean Bourhis, Anne Aupérin, Benjamin Lacas, Jean-Pierre Pignon, Ellen Benhamou, Somvilai Chakrabandhu, Anthony TC Chan, Qiu-Yan Chen, Yong Chen, Richard J Chappell, Horace Choi, Daniel TT Chua, Melvin Lee Kiang Chua, Julian Higgins, Ming-Huang Hong, Ruey-Long Hong, Edwin Pun Hui, C.F. Hsiao, Michael Kam, Georgia Angeliki Koliou, Dora LW Kwong, Shu-Chuan Lai, Ka On Lam, Michael L LeBlanc, Anne WM Lee, Ho Fun Victor Lee, Wen Fei Li, Brigette Ma, Frankie Mo, James Moon, Wai Tong Ng, Brian O'Sullivan, Claire Petit, Jean Pierre Pignon, Sharon X. Poh, Gerta Rücker, Jonathan Sham, Yoke Lim Soong, Ying Sun, Terence Tan, Lin-Quan Tang, Yuk Tung, Joseph Wee, Xuang Wu, Tingting Xu, Yuan Zhang, and Guopei Zhu
Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC. Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified. Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect. Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.